# Molecular Mechanisms of Arterigenesis

> **NIH NIH P01** · YALE UNIVERSITY · 2022 · $1,912,161

## Abstract

The overall goal of this Program Project is to understand molecular mechanisms regulating
arteriogenesis that may be exploited as potential treatments for vasoocclusive cardiovascular
diseases including coronary artery disease, peripheral arterial disease and cerebrovascular
disease. We have assembled a multidisciplinary team of highly accomplished PIs with diverse
backgrounds (cardiology, cell biology, biomechanical engineering, pharmacology) to investigate
key molecular events that lead to development and growth of arterial vasculature. The in-depth
understanding of these mechanisms can then be parlayed into development of novel
therapeutic modalities for this important group of cardiovascular diseases. Together, our studies
will define the key events leading to arterial vessel growth and will lead to the development of
new therapies.
PPG Aims are:
 Aim 1. Elucidate how ERK signaling controls arteriogenesis (Project 1).
 Aim 2. Unravel the role of the miR 17-92 cluster in controlling arteriogenesis and its
 regulation and interaction with ERK signaling (Project 2
 Aim 3. Determine how fluid shear stress and changes in the extracellular matrix activate
 ERKs and other signaling pathways that mediate arteriogenesis, and identify restriction
 points that impair arteriogenesis in disease (Project 3).
Relevance to Public Health: Coronary artery disease and peripheral artery disease are major
causes of illness and death in developed nations. Poor arteriogenesis is a critical determinant of
these diseases and in patients’ recovery after myocardial infarction. This application proposes to
elucidate the signaling network that governs flow-dependent vessel remodeling and test two
new directions for improving arteriogenesis. These studies include testing whether activating an
arteriogenic signaling pathway improves arteriogenesis in disease models. They have the
potential to identify new targets and new reagents for therapy, as well as to achieve a deeper
understanding of the fundamental biology that will form the basis for future studies.

## Key facts

- **NIH application ID:** 10433814
- **Project number:** 5P01HL107205-10
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Michael Simons
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,912,161
- **Award type:** 5
- **Project period:** 2012-02-10 → 2024-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10433814

## Citation

> US National Institutes of Health, RePORTER application 10433814, Molecular Mechanisms of Arterigenesis (5P01HL107205-10). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10433814. Licensed CC0.

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